Receptor-mediated activation was analyzed in T and B lymphocytes from normal mice and from mice infected with the MAIDS-inducing defective murine leukemia virus. Several weeks after viral infection, the proliferative responses of T and B cells to cross-linking of TCR and sIg respectively were significantly reduced despite the expression of normal surface levels of these receptors by most T and B cells. To analyze early signaling events in these cells, [Ca2+]i was measured in response to surface receptor cross-linking. The [Ca2+]i responses of both T and B cells from MAIDS-infected mice were decreased. B cell responses to sIg cross-linking were further analyzed by examining protein tyrosine phosphorylation induced by sIg cross-linking. It was found that after virus infection, there was a progressive loss of selected tyrosine phosphorylation events with conservation of other events. The response defect in B cells from MAIDS mice is thus reflected in selected alterations of tyrosine phosphorylation in response to sIg signaling. Costimulatory B7 molecules (B7-1 or CD80; and B7-2 or CD86) are known to bind to T cell costimulatory receptors CD28 and CTLA4. Engagement of CD28 is know to transduce signals in T cells that play a critical role in T cell activation; however, little is known of the ability of B7 molecules to themselves act as signal transducing molecules. The effect of B7-1 and B7-2 crosslinking was assessed in the B cell lymphoma BAL.17. Initial studies demonstrated that B7 crosslinking induces AP-1 components including c-fos and c-jun, as demonstrated by gel retardation and "super-shift" assays. These findings indicate that B7 engagement by counter-receptors such as CD28 or CTLA4 may lead to bidirectional effects, functioning to transduce signals in B7-expressing cells such as B lymphocytes, in addition to signaling CD28/CTLA4 positive T cells.